Pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil administration after major hepatectomy in a rat model

Cancer Chemotherapy and Pharmacology - Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired...     

Additional Effect of Visceral Fat Resection in an Obese Rat Model of Gastric Banding

Background  There is accumulating agreement that bariatric surgery is currently the most efficacious and enduring treatment for clinically severe obesity, and as a result, the number of bariatric surgeries performed worldwide has increased in recent years. Although the function of visceral fat has gradually become clear, the effect of visceral fat resection is still unknown. The aim of this study was to clarify the additional effect of visceral fat resection in an obese rat model of gastric banding. Methods  Forty male Zucker fatty rats were divided into four groups: the control group, visceral fat resection group, gastric banding group, and gastric banding with visceral fat resection group. They were followed for 8 weeks after surgery, and their body weight change, cumulative food intake, metabolic parameters, and adipocytokines were measured. Results  The gastric banding rats either with or without visceral fat resection showed significant decreases in weight gain, cumulative food intake, and levels of metabolic parameters compared to the control rats. There were no significant differences in weight gain and cumulative food intake between gastric banding with and without visceral fat resection. However, gastric banding with visceral fat resection resulted in lower plasma levels of free fatty acid and TNF-alpha compared to gastric banding alone, and expression of adiponectin mRNA in the adipose tissue was significantly decreased with the addition of visceral fat resection compared with banding alone. There were no significant differences in any parameters between controls and rats receiving visceral fat resection alone. Conclusion  Visceral fat resection may improve adipocytokines and free fatty acid in an obese rat model of gastric banding. However, further studies are necessary before the procedure can be considered an option on bariatric surgery.     

A case of retroperitoneal mucinous cystadenoma treated successfully by laparoscopic excision

A case of retroperitoneal mucinous cystadenoma treated laparoscopically is reported. A 26-year-old woman, who complained of abdominal fullness, was referred to us after a large intra-abdominal mass was discovered at her local hospital. Ultrasound and computed tomography showed a fluid-filled mass, 9 cm in diameter, in the left retroperitoneal space. Laparoscopic surgery was performed. We found a smooth and thin-walled cystic tumor that displaced the descending colon to the right and arose from the retroperitoneum, loosely adhering to the psoas muscle. We successfully extirpated the tumor laparoscopically. The surgical specimen consisted of a multilocular, red to yellowish-gray, cystic mass with a smooth, glistening external surface, and inner lining. The mass was filled with thin, yellowish fluid. The histologic diagnosis was benign mucinous cystadenoma. The postoperative course was uneventful, and the patient remains free of recurrence 15 months after surgery. Retroperitoneal mucinous cystadenoma is a rare entity, and the treatment of choice is surgical excision. Laparoscopic extirpation should be considered for the treatment of selected retroperitoneal cystic lesions.     

Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer

Previously, we have reported that gain at chromosome 20q13 is the most common genomic copy number aberration in gastric cancer (GC) (29/30 cases), and that among the genes located in this region, we have identified DDX27, whose expression level shows the highest correlation with genomic copy number, as a candidate therapeutic target for GC. Here, we analyzed the clinicopathological significance of DDX27 using immunohistochemistry and studied its functions using knockdown assays. We found that DDX27 was frequently upregulated in GC tissues (98 of 140 cases, 70%), and significantly associated with venous invasion and liver metastasis. Furthermore, multivariate analysis of GC patients showed that high expression of DDX27 was independently associated with poorer prognosis. In functional assays, knockdown of DDX27 reduced the ability of GC cells to form colonies both on conventional plates and soft agar, but had little effect on their invasiveness. We also found that knockdown of DDX27 reduced the viability of GC cells through inhibition of cell cycle progression independently of apoptosis. Interestingly, DDX27 depletion induced accumulation of TP53 in a TP53 wild-type cell line, AGS, but not in a TP53-deleted cell line, 44As3, although DDX27 knockdown commonly reduced the viability of both, indicating the TP53-dependent and independent cell cycle control of DDX27. Thus, our results suggest that expression of DDX27 contributes to colony formation by GC cells through cell cycle control and may be a potential therapeutic target for GC patients with chromosome gain at 20q13.     

Efficacy of rebamipide for low-dose aspirin-related gastrointestinal symptoms

Gastrointestinal symptoms are a problematic issue for patients who take low-dose aspirin for long time. We conducted a pilot study to investigate the efficacy of combination therapy with proton pump inhibitor and rebamipide. This was a prospective, randomized, double-blind, placebo-controlled cross-over study. All the subjects received aspirin 100 mg and omeprazole 20 mg. The subjects were divided into two groups and received either rebamipide 300 mg or placebo, which was prescribed for 4 weeks. The subjects were instructed to record their gastrointestinal symptom rating scale before the study and 1 and 4 weeks after beginning the protocol. These scores of the groups were compared before and after the treatment to evaluate the severity of their symptoms and the number of symptom items present in each group. For the subjects receiving rebamipide, the total prevalence of lower gastrointestinal symptoms was significantly different from the placebo group (p=0.0093) at week 4. No troublesome symptoms were observed in the rebamipide group. Inconclusion, the administration of rebamipide prevented the occurrence of troublesome symptoms, especially lower gastrointestinal symptoms, in patients taking aspirin and omeprazole. Rebamipide is a candidate drug for combination therapy with proton pump inhibitors to prevent low-dose aspirin-induced gastrointestinal symptoms.     

Calcification of degenerating tissues in the periodontal ligament during tooth movement

OBJECTIVE: Calcification of degenerating tissues in the periodontal ligament (PDL) during tooth movement was investigated longitudinally. MATERIALS AND METHODS: Upper first molars of male Wistar rats were moved lingually for 1, 7 and 21 d, following which unfixed undecalcified sections of the lingual PDL (in the pressure zone) were examined histologically, histochemically (autoradiography and electron probe microanalysis). RESULTS: On d 1 of tooth movement, degenerating tissues, together with some calcified particles, were visible in the pressure zone of the lingual PDL. On d 7, substantial calcified aggregations were seen in the degenerating tissues, predominantly situated between the bone and root. This was confirmed by the 45Ca autoradiography. On d 21 of tooth movement, large calcified aggregations were still clearly evident between the bone and root. CONCLUSIONS: This calcification of the degenerating tissues is a self-defense response of the living body to prevent direct contact between alveolar bone and the tooth root during compression of the PDL, so preventing friction between them and the development of ankylosis.